4.4 Article

The effect of transient increases in kynurenic acid and quinolinic acid levels early in life on behavior in adulthood: Implications for schizophrenia

期刊

SCHIZOPHRENIA RESEARCH
卷 150, 期 2-3, 页码 392-397

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ELSEVIER SCIENCE BV
DOI: 10.1016/j.schres.2013.09.004

关键词

Schizophrenia; Glia; Attention; Learning; Memory; Social

资金

  1. NIH [R01DA027688]

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Kynurenic acid is a tryptophan metabolite that is synthesized and released in the brain by astrocytes and acts as an antagonist of nicotinic acetylcholine receptors and N-methyl-D-aspartate glutamate receptors, both of which are critically involved in cognition as well as neural plasticity and brain development. The concentration of kynurenic acid is increased in the brains of persons with schizophrenia and this increase has been implicated in the cognitive and social impairments associated with the disease. In addition, growing evidence suggests that the increase in kynurenic acid may begin early in life. For example, exposure to influenza A virus during development results in a transient increase in kynurenic acid concentration that could disrupt normal brain development and lead to cognitive deficits later in life. Changes in kynurenic acid may thus provide a link between developmental exposure to viruses and the increased risk of subsequently developing schizophrenia. To test this, we mimicked the effects of influenza A exposure by treating rats with kynurenine, the precursor of kynurenic acid, on postnatal days 7-10. We observed a transient increase in both kynurenic acid and quinolinic acid during treatment. When rats were subsequently behaviorally tested as adults, those previously treated with kynurenine exhibited decreased social behavior and locomotor activity. In contrast, attentional function and fear conditioning were not affected. Together with other recent findings, these data have several implications for understanding how viral-induced changes in tryptophan metabolism during development may contribute to schizophrenia-related symptoms later in life. (C) 2013 Elsevier B. V. All rights reserved.

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